The specific aims of Subproject I are to examine: 1) factors (genetic, environmental, allergic, immunologic, physiologic, etc.) which may predispose to lower respiratory tract infections (LRIs) in early childhood and 2) the relationship of such factors and LRIs to the subsequent development of chronic airways disease in later life. These inter-relationships have been, and will continue to be, studied prospectively in a cohort of over 1,200 infants who, together with their parents and siblings, have been followed from the time of birth of the index subjects. Baseline lung function, airway reactivity, immunologic studies (humoral and cellular), allergy skin tests, and passive smoke exposure (cotinine levels) are assessed. Similar evaluations will be done on the parents and siblings during follow-up. These studies will allow us to determine prospectively and longitudinally the major factors relating to the development of chronic obstructive airways disease during childhood and young adult life and, thereby, allow us to determine the best methods of preventing such chronic disease. (e.g., better immunizations, environmental changes, appropriate counseling, drug therapy,) The purposes of Subproject II are to continue: 1) the development of pulmonary function tests applicable to the uncooperative infant and young child; and 2) the assessment of the physiologic growth and development of the human lung and how this growth may be altered by disease processes. In order to determine how lung diseases and risk factors in early life may predispose to chronic lung disease, it is essential to have reliable non-invasive tests of lung function applicable to infants and young children. Newer methods of studying the compliance and resistance of the lung and total respiratory system in young infants will be assessed. The use of lung sounds to reflect lung function in uncooperative infants will be studied in detail. The relationship of maternal smoking during pregnancy to lung function in the first few months of life will be examined, especially with respect to levels of elastin and elastase in the umbilical cord artery (potentially reflecting the amount of lung elastin). Longitudinal studies will examine the normal physiologic growth pattern of lung function in the first 12-18 months of life and how this may be altered by LRIs. Recovery patterns from acute bronchoconstriction will be studied in normal and asthmatic boys and girls to evaluate sex-related changes in airway dilation patterns following bronchoconstriction.